A Method to screen U.S. environmental biomonitoring data for race/ethnicity and income-related disparity

BACKGROUND: Environmental biomonitoring data provide one way to examine race/ethnicity and income-related exposure disparity and identify potential environmental justice concerns. METHODS: We screened U.S. National Health and Nutrition Examination Survey (NHANES) 2001–2008 biomonitoring data for 228 chemicals for race/ethnicity and income-related disparity. We defined six subgroups by race/ethnicity—Mexican American, non-Hispanic black, non-Hispanic white—and income—Low Income: poverty income ratio (PIR) <2, High Income: PIR ≥ 2. We assessed disparity by comparing the central tendency (geometric mean [GM]) of the biomonitoring concentrations of each subgroup to that of the reference subgroup (non-Hispanic white/High Income), adjusting for multiple comparisons using the Holm-Bonferroni procedure. RESULTS: There were sufficient data to estimate at least one geometric mean ratio (GMR) for 108 chemicals; 37 had at least one GMR statistically different from one. There was evidence of potential environmental justice concern (GMR significantly >1) for 12 chemicals: cotinine; antimony; lead; thallium; 2,4- and 2,5-dichlorophenol; p,p’-dichlorodiphenyldichloroethylene; methyl and propyl paraben; and mono-ethyl, mono-isobutyl, and mono-n-butyl phthalate. There was also evidence of GMR significantly <1 for 25 chemicals (of which 17 were polychlorinated biphenyls). CONCLUSIONS: Although many of our results were consistent with the U.S. literature, findings relevant to environmental justice were novel for dichlorophenols and some metals

Unexpected Long-Term Variability in Jupiter's Tropospheric Temperatures

An essential component of planetary climatology is knowledge of the tropospheric temperature field and its variability. Previous studies of Jupiter hinted at periodic behavior that was non-seasonal, as well as dynamical relationships between tropospheric and stratospheric temperatures. However, these observations were made over time frames shorter than Jupiter's orbit or they used sparse sampling. We derived upper-tropospheric (300-mbar) temperatures over 40 years, extending those studies to cover several orbits of Jupiter, revealing unexpected results. Periodicities of 4, 7 8-9 and 10-14 years were discovered that involved different latitude bands and seem disconnected from seasonal changes in solar heating. Anti-correlations of variability in opposite hemispheres were particularly striking at 16, 22 and 30 degrees from the equator. Equatorial temperature variations are also anticorrelated with those 60-70 km above. Such behavior suggests a top-down control of equatorial tropospheric temperatures from stratospheric dynamics. Realistic future global climate models must address the origins of these variations in preparation for their extension to a wider array of gas-giant exoplanets.Comment: Primary file: 16 pages, 5 figures. Supplemental File (attached): 12 pages, 3 figures, 1 tabl

The Back Pain Consortium (BACPAC) Research Program Data Harmonization: Rationale for Data Elements and Standards

ObjectiveOne aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses.MethodsConsortium-wide working groups established harmonized data elements to be collected in all studies and developed standards for tabular and nontabular data (eg, imaging and omics). The BACPAC Data Portal was developed to facilitate research collaboration across the Consortium.ResultsClinical experts developed the BACPAC Minimum Dataset with required domains and outcome measures to be collected by use of questionnaires across projects. Other nonrequired domain-specific measures are collected by multiple studies. To optimize cross-study analyses, a modified data standard was developed on the basis of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model to harmonize data structures and facilitate integration of baseline characteristics, participant-reported outcomes, chronic low back pain treatments, clinical exam, functional performance, psychosocial characteristics, quantitative sensory testing, imaging, and biomechanical data. Standards to accommodate the unique features of chronic low back pain data were adopted. Research units submit standardized study data to the BACPAC Data Portal, developed as a secure cloud-based central data repository and computing infrastructure for researchers to access and conduct analyses on data collected by or acquired for BACPAC.ConclusionsBACPAC harmonization efforts and data standards serve as an innovative model for data integration that could be used as a framework for other consortia with multiple, decentralized research programs

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10(-8)), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10(-12)) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10(-10)). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants;thirteen of the chronotype signals remained associated at P<5x10(-8) on meta-analysis and eleven of these reached P< 0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10(-8)). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10(-16)) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10(-9);and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10(-9)). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05);undersleeping and BMI (rG = 0.147, P = 1x10(-5)) and over-sleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Polymorphic variants of genes involved in homocysteine metabolism in celiac disease

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape